The intensity or vigor of goal-directed behavior is a correlate of the motivation underlying it, and, therefore, motivation can be inferred by monitoring the performance of goal-directed behavior. To study motivated behavior in monkeys, we use a task in which monkeys must perform some work, in this case detecting when a target spot turns from red-to-green, to obtain a drop of juice. In one set of tasks, a visual stimulus, a cue, indicates how much discomfort must be endured, e.g., the number of trials to be worked, to obtain the reward. The monkeys learn about the cues quickly, often after just a few trials. We have shown previously that for normal monkeys a simple mathematical relation describes how reward size, delay and satiation level affect motivation: errors = (1+kD)/ ((aR) F(S)). k is a constant, D is the delay, a is another constant, R is reward size (in drops), and F(S) is a sigmoidal funtion of satiation, which is 1-thirst. These results are consistent with temporal discounting of reward with time. In this form there is no interactive effect between satiation level and incentive value on motivation. Thirst simply enhances the incentive value, and reward is discounted as a hyperbolic function of delay duration as shown before in choice tasks. This model gives us an extended view of how incentive and motivational values are calculated and represented in the brain. For the roles of orbitofrontal and lateral prefrontal cortices in this relation, lateral orbitofrontal lesions impaired monkeys performance as a function of reward delay duration and reward size. All three OFC lesioned monkeys were less sensitive than controls to the range of expected reward sizes. Error rates still decreased as the expected reward size increased, but the differences between the maximum and minimum error rates were smaller than seen with normal monkeys. ANOVA showed a statistically significant main effect of reward size, and a significant interaction. There was also a statistically significant main effect of delay. All three OFC monkeys also displayed abnormal error rate patterns across the range of expected delay durations and reward sizes, when these variables were combined. Thus, when compared to the normal animals described in the preceding paragraph, the OFC lesioned monkeys have difficulty in adjusting their behavior is situations where there are different amounts of reward discounting, and indeed, the data from these monkeys is not well-fit by the equations discovered for the normal monkey behavior. In contrast, 3 monkeys with lateral prefrontal cortex removals had behavior that was indistinguishable from the normal monkeys when tested with the reward size or reward postponement conditions. Surprisingly, however, when the monkeys with the LPFC ablations were tested in the condition where both reward size and delay were varied simultaneously, the LPFC lesioned monkeys had abnormal behavior that was indistinguishable from that seen with OPFC lesioned monkeys. This raises the possibility that the lateral prefrontal cortex is playing an essential role with the discounting from two different sources must be combined, but the orbital frontal cortex plays an essential role in assessing any modification of reward value. Motivation includes hedonic and incentive dimensions, and its regulation relies on a constant interaction between internal processes and changes in the environment. To study neuronal processes underlying these two aspects of motivation, we recorded the activity of single neurons in orbital and ventromedial regions of the prefrontal cortex in behaving monkeys. Neurons in both regions were more sensitive to hedonic than to incentive aspects of motivation. The orbitofrontal neurons were more involved in externally triggered processes and the ventromedial neurons in internal motivational processes. Thus, different aspects of hedonic motivation preferentially engage orbital and ventromedial prefrontal cortices, which could underlie the differential implication of these regions in major psychiatric disorders. We recorded 355 neurons from the prefrontal cortex of two monkeys. The responses of the neurons in OFC were compared to those in VMPFC. The activity profiles were similar in the 2 animals so the data were pooled. In Cued trials, 112 and 121 neurons were recorded from OFC and VMPFC, respectively. In Self-Initiated trials, 70 and 74 neurons were recorded from OFC and VMPFC, respectively. Neuronal activity was affected by both Reward Size (1, 2 or 4 drops) and Action (passive vs active trials) factors in Cued trials and by the Reward Size in Self-Initiated trials. In Cued trials, we compared the effects of Reward Size and Action on spike counts for each neuron. At cue onset, the encoding of the Reward Size factor engaged a larger proportion of neurons and accounted for more variance than the encoding of the Action factor. The encoding of the Action factor became more prominent during the course of a trial with a sharp increase in the proportion of neurons encoding Action at the feedback (supplementary fig 3). This pattern is reminiscent of lipping behavior, a Pavlovian response that is sensitive to Reward Size at cue onset and to Action at the feedback, supporting the idea that neuronal activity in ventral prefrontal cortex reflects the hedonic value of these events. To encode incentive aspects of motivation, neurons should respond to reward size only in Cued-Active trials, that is, they should display a specific type of interaction between Reward size and Action factors in the ANOVA, with firing rate being affected by Reward Size only in Cued-Active trials (supplementary Figure 4). The average proportion of neurons showing such a pattern was not above the number expected by chance (7.3 1% in OFC, 4.8 1% in VMPFC). Thus, the activity of ventral prefrontal neurons seems more closely related to hedonic than to incentive aspects of motivation. Although neurons in both subregions, OFC vs VMPC, showed this general trend, response in the two regions were different. The encoding of Reward Size appeared earlier in OFC, engaged a larger proportion of neurons, and accounted for more variance than in VMPFC. Although at the feedback, neurons in both regions became more sensitive to the Action factor, the increase in proportion of neurons encoding Action began earlier in VMPFC (at the feedback) than in OFC (after the feedback). Moreover, in OFC, the strength of the signal (% variance explained) related to the Reward-Size factor remained higher than the strength of the signal related to the Action factor, whereas in VMPFC, at the feedback, the strength of the signal related to Action became as strong as the signal related to Reward Size (fig 3, center, and supplementary fig 3). These differences suggest that the way in which neurons encode hedonic value is quite different in these two subregions: at the cue, when hedonic value is determined based on stimulus-reward associations, and this encoding occurs earlier in OFC. At the feedback, when hedonic value depends more critically upon how the reward can be obtained (whether an action is needed or not), the encoding begins earlier in VMPFC.